Of 1327 totally synthetic drugs marketed worldwide today, 528 are chiral. Often, only one enantiomer of a chiral drug provides the desired pharmacological action. the opposite enantiomer may have toxic or other harmful effects. Thus, syntheses that give racemic drugs are wasteful and potentially dangerous. Surprisingly, only 61 of the 528 synthetic chiral drugs are sold in non-racemic form. Thus, new FDA regulations on chiral drugs will be proposed shortly, and optical purity has become a major issue in pharmaceutical synthesis. Also, the common use of chiral excipients (supposedly inactive fillers) in medicines (e.g., lactose, cellulose, cyclodextrins), and the possibility of effects upon the dissolution or absorption of enantiomers, should be noted. The tow principal goals of this project are: (1) to develop general methods for the enantioselective synthesis of organic compounds using chiral transition metal reagents (auxiliaries) and catalysts, and (2) to elucidate mechanisms and establish underlying general principles of metal-based chirality transfer (which are in most cases only rudimentarily understood). The study of chiral pseudotetrahedral organorhenium complexes (n5- C5R5)Re(NO)(PPh3)-(X) will be emphasized. These compounds are easily synthesized in optically pure form and are generally air and configurationally stable. Numerous reactions have been discovered in which the rhenium-centered chirality is stereospecifically transferred to a new ligand-based chiral center. In one approach, the [(n5-C5R5)Re(NO)(PPh3)]+ moiety functions as a "chiral Lewis Acid" that binds and activates substrates with a high (thermodynamic) degree of "chiral recognition." Through labeling experiments, conformational studies, X-ray crystallography, and MO calculations, we seek to define the mechanistic basis for asymmetric induction. Synthetic objectives include the development of new (a) catalytic and stoichiometric methods for the asymmetric addition of nucleophiles to aldehydes, ketones, alkenes, and unsaturated nitrogen-containing compounds, and (b) catalytic and stoichiometric cycloadditions, conjugate additions, and electrophilic additions involving multiply unsaturated ligands or relatives thereof. From this program of fundamental research, improved syntheses of several types of medicinally important compounds will be realized.